Post Approval Procedures

H. Post Approval Procedures

Approval is not the end of the relationship with the IRB. The IRB presumes that the protocol is being implemented exactly as approved and without any problems. It is the investigator's responsibility to keep the IRB informed of significant problems or violations of protocol.

1. Continuing Review

The person listed as the Principal Investigator is responsible for submitting a renewal request prior to the stated expiration date. The designated investigator for each site will be sent a courtesy renewal reminder notice approximately 60 days prior to the expiration date. Each designated investigator is responsible for gathering all information from that site and sending it to the primary or initial principal investigator to compile.

OPRR Reports 95-01

The major question asked during continuing review is whether, in light of the information gathered since the last review, the members would again conclude that approval is appropriate. The type of information sought is:

A summary of the activity during the approval period

The status of the study

Open to enrollment,

Closed to enrollment, treatment continuing, or

Follow-up monitoring only.

The number of participants

Number enrolled,

Number still in study,

Number withdrawn,

Number lost to follow-up

A summary of adverse events and safety reports and whether the risk assessment has changed (Safety Letters, etc.)

Number and type of adverse events at this location.

Last report by Data Safety Monitoring Board (DSMB).

Whether the expectation of benefit from the study to society or to subjects has changed.

Whether the alternatives to participation have changed and

Whether there is any new information about qualification of the investigator or the site

FDA audit reports

Sponsor monitoring reports

Information about the consent process.

The most frequent question raised

The person most often giving information and gaining consent

2. Adverse Event Reports

Adverse Events (AEs) are new findings or unexpected problems whose nature, severity, and frequency are not described in the information provided to the IRB or to study participants. AEs may cause or increase the risk of physical or psychological harm to the research participant or others.

AE information is generated from two sources:

Adverse Event Reports (Internal Events): Events that occur locally within studies approved by this IRB, and

Safety Reports (External Events): Adverse events reported from other sites that are sent to the sponsor and are then forwarded to the NGHS investigator for transmission to the IRB. Ideally the data center provides useful evaluative information.
A report summarizing information provided to the investigator via SRs will be submitted as a part of the materials required for continuing review. However, if at any time, prior to a study’s expiration date, the study’s sponsor and/or the FDA issues an "Action Letter" related to any experimental and / or investigational component of a study requiring:

Notification of the study’s participants of new information or insights necessitating changes,
the investigator is required to submit the SR(s) and the modification(s) to the IRB for review and approval prior to implementation.

The IRB considered a risk/benefit ratio based on information available at the time the protocol was submitted. New safety information could impact this ratio and could affect an IRB's judgment about whether continued approval is warranted.

Participants are informed about any reasonably foreseeable risks and are told that they will be informed of any significant new information that might affect their decision. New information about safety might need to be transmitted to participants.

Recognizing, reporting and rectifying problems, AEs safeguard the rights and well-being of human subjects involved in research and ensure regulatory compliance.

Types of Adverse Events :

Expected Adverse Event - Events (side effects/risks) that are reported in the study’s protocol, Investigators’ Brochure and/or included in the informed consent. Expected AEs need not be reported to the IRB. The reporting requirements of adverse events to the FDA and/or the study sponsor are not affected by this policy. Please contact the study sponsor or the FDA with questions concerning adverse event reporting requirements.

Unexpected AE – An adverse event that is unanticipated (not noted in the consent or Investigator's Brochure) or that is more serious than anticipated. The IRB requires investigators to report each unexpected event in writing, within five (5) working days of the event.

Serious Adverse Event (SAE) – An event, expected or unexpected, that: is fatal or life-threatening; is permanently or significantly disabling; requires or prolongs inpatient hospitalization; or, is a congenital anomaly, cancer, or overdose. SAEs should be reported to NGHS IRB immediately (within 24 hours of occurrence) via e-mail, with formal written notification to follow within 5 working days of the event.

21 CFR 312.53(c)(vii) and .66

Reporting Adverse Events:

Unexpected AEs and SAEs must be reported in writing within five (5) working days using the AE Report Form. This form must be completed and signed by the Principal Investigator. Although an electronic submission is acceptable, a signed, hard-copy is required as follow-up to the electronic submission.

AEs will be reviewed by the IRB Chair or his/her designee and will be reported to the full IRB at the next scheduled meeting via the ‘Standing Report’ provided at IRB Meetings.

Action will be taken if the new information changes the risk/benefit evaluation or if the new information should be conveyed to currently enrolled subjects and should be included in a modified consent form. The IRB chair shall have the authority to temporarily stop the study until the IRB can be convened if there is a reasonable risk of a previously unanticipated harm to other subjects.

Following review of the AE report, a copy of the report, reflecting the action(s) of the IRB, will be provided to the investigator and/or the investigator’s research staff.

3. Changes In Or From Protocol

A protocol should be implemented exactly as it was approved. The IRB should never be surprised to learn that something has occurred that is not in compliance with the protocol.

21 CFR 56.108a(4)

Modifications (changes to the "research plan")
Modifications are changes to the written protocol document; the change applies to all sites and all subjects. They are generated by the research base/sponsor. The integrity of the study is maintained.

Violations Of The Protocol (changes to the "research activity")
Protocol violations are usually taken to accommodate to the needs of an individual patient. They change the "activity" within an approved protocol.

There are two types:

Exceptions: These are prospectively considered violations that are accepted by the sponsor.

For Example:

A subject knows that he/she will be 5 days late for the next appointment due to an important trip. The sponsor is notified and agrees

Deviations: These are unexpected violations.

For Example:

A subject gets the flu and is 5 days late for the next appointment. The sponsor is notified after the fact.

All violations must be summarized on the continuing review application.

Violations that affect the safety or well being of a subject or that occur with sufficient frequency must be reported to the IRB.

Violations submitted to the IRB will be acknowledged.

The chair is authorized to seek supplemental or clarifying information.

Emergency Changes From Protocol
A violation to protocol made to respond to the emergency needs of a subject or of all subjects; that is, to reduce their risk of harm, should be reported to the IRB in the same format used for reporting to the sponsor/research base and in the same time span.

4. Report From FDA Clinical Investigator Audit

The IRB will require each investigator to report the results of any clinical investigator audit performed by an investigator of the FDA.